(1) Field of the Invention
The present invention relates to an enhancer comprising a spherical carbon as an active ingredient for augmenting the antianemia effect of erythropoietin, especially recombinant erythropoietin (recombinant human EPO: hereinafter sometimes referred to as "rHuEPO").
(2) Description of the Related Art
Through the development of gene engineering, rHuEPO preparations came to be used for treating anemia. Erythropoietin is one of the erythropoiesis-stimulating factors existing in a living body; the shortage of erythropoietin is one cause of anemia. The rHuEPO has been chemically, immunologically, and biologically confirmed to be identical to human erythropoietin.
The rHuEPO is a glycoprotein with a molecular weight of approximately 30,000 containing 165 amino acid residues which have two internal disulfide bonds linking the positions 7 and 161 and positions 29 and 33 and wherein three N-glucoside type saccharide chains are bound to the 24th, 38th, and 83rd asparagines and one O-glucoside type saccharide chain is bound to the 126th serine. There are some rHuEPOs dependent on the structures of saccharide chains. Examples of rHuEPOs that are now available commercially are Epogen.TM. and Espo.TM.. (See Seigo IWAKAWA, IGAKUNO AYUMI, Vol. 155, No. 10, pp. 631-633, 1990.)
Usually, when anemia becomes severe, the concentration of erythropoietin in blood becomes high. In renal anemia patients, however, in comparison with anemia patients having a normal renal function, there are not only many cases wherein the concentration of erythropoietin in blood is low, but also there are many cases wherein the erythropoiesis-inhibiting factor is present. Thus, a large amount of rHuEPO is needed in order to increase hematocrit as expected.
The rHuEPO causes, however, side effects such as hypertension, headaches, hypertensive encephalopathy, cerebral infarctions or myocardial infarctions due to thrombosis, closure of the retinal venous, obstruction of shunts, or lowering of dialysis efficiency. In addition, allergic or anaphylaxis-like symptoms of rHuEPO, such as lowering of blood pressure, arthralgia, itching, edema, red eyes, oppressive feeling in the chest, bleeding fleck, etc., are observed. Further, transitory and slight pyrexia, rashes, or hepatic disorders may sometimes be observed. Hypertension due to side effects is believed to be caused by the increase in peripheral blood vessel resistance due to the constriction of the peripheral blood vessel and the rise in blood viscosity.